Wang Limin, Wang Dawei, Xing Bowen, Tan Ying-Cai, Huang Jianyun, Liu Bingqian, Syrovatkina Viktoriya, Espenel Cedric, Kreitzer Geri, Guo Lin, Zhang J Jillian, Huang Xin-Yun
Department of Physiology and Biophysics, Cornell University, Weill Cornell Medical College, NY, New York 10065, United States.
Department of Cell and Developmental Biology, Cornell University, Weill Cornell Medical College, NY, New York 10065, United States.
J Mol Biol. 2017 Dec 8;429(24):3836-3849. doi: 10.1016/j.jmb.2017.10.020. Epub 2017 Oct 25.
Heterotrimeric G-proteins are essential cellular signal transducers. One of the G-proteins, Gα, is critical for actin cytoskeletal reorganization, cell migration, cell proliferation, and apoptosis. Previously, we have shown that Gα is essential for both G-protein-coupled receptor and receptor tyrosine kinase-induced actin cytoskeletal reorganization such as dynamic dorsal ruffle turnover and cell migration. However, the mechanism by which Gα signals to actin cytoskeletal reorganization is not completely understood. Here we show that Gα directly interacts with Abl tyrosine kinase, which is a critical regulator of actin cytoskeleton. This interaction is critical for Gα-induced dorsal ruffle turnover, endothelial cell remodeling, and cell migration. Our data uncover a new molecular signaling pathway by which Gα controls actin cytoskeletal reorganization.
异源三聚体G蛋白是重要的细胞信号转导分子。其中一种G蛋白Gα,对于肌动蛋白细胞骨架重排、细胞迁移、细胞增殖和细胞凋亡至关重要。此前,我们已经表明Gα对于G蛋白偶联受体和受体酪氨酸激酶诱导的肌动蛋白细胞骨架重排(如动态背侧褶皱周转和细胞迁移)都是必不可少的。然而,Gα向肌动蛋白细胞骨架重排发出信号的机制尚未完全了解。在这里,我们表明Gα直接与Abl酪氨酸激酶相互作用,Abl酪氨酸激酶是肌动蛋白细胞骨架的关键调节因子。这种相互作用对于Gα诱导的背侧褶皱周转、内皮细胞重塑和细胞迁移至关重要。我们的数据揭示了一条新的分子信号通路,通过该通路Gα控制肌动蛋白细胞骨架重排。